A Comparative Study: Evaluation of Antioxidant Activity of Melatonin and Some Indole Derivatives

To understand antioxidant activity and the role played by melatonin, we have designed and tested several new compounds. We present the results in terms of structure-activity relationships, focusing on the lack of the methoxy group and the influence of the amide side chain. Antioxidant activity of melatonin and some new melatonin analogue indole derivatives were investigated, using lipid peroxidation and superoxide anion radical scavenger activity assays, in rat liver tissue homogenate. Most of the compounds were found to be very potent inhibitors of malondialdehyde (MDA) formation at 10⁻³M. Inhibition rates ranged from 75-44 %. However, no significant inhibitory effect was obtained on superoxide anion formation. Consequently, it can be concluded that these compounds exhibit important LP activity compared to melatonin.     

Comparison of forced-air warming systems in prevention of intraoperative hypothermia

In this study, we aimed to compare the effects of forced-air warming upper body blankets and forced-air warming underbody blankets on intraoperative hypothermia in patients who were planned to undergo open abdominal surgical operations in which extensive heat loss occurs. This prospective and randomized study included 92 patients who would undergo lower abdominal surgery under general anesthesia. Patients were randomized by closed envelope method and divided into two groups. Group I (n:46) included the patients who would receive warming with forced-air warming upper body blanket, and Group II (n:46) consisted of the patients who received warming with forced-air warming underbody blanket. Central body temperature was recorded by measuring with a temperature probe placed in distal esophagus. Demographic data, amount of fentanyl, crystalloid and blood products used, duration of operation, type of operation, hemodynamic parameters, shivering and thermal damage information were recorded. There was not any statistically significant difference among the patients in terms of demographic data, amount of fentanyl, crystalloid and blood products used, duration and type of operation and hemodynamic parameters. No difference was found between the groups in terms of body temperatures (Group I:36.1?°C, Group II:36.3?°C, respectively) (P?>?0.05). Forced air warming underbody blanket can be as effective as forced-air warming upper body blankets in preventing intraoperative hypothermia. They can be alternative in cases where use of forced-air warming upper body blankets is not feasible.     

<Emphasis Type="SmallCaps">l</Emphasis>-Carnitine: a new insight into the pathogenesis of endometrial cancer

Objectives

The present study aims to specify the role of l-carnitine in the pathogenesis of endometrial cancer by comparing the serum total l-carnitine levels of endometrial cancer patients with those of healthy women.

Methods

Serum total l-carnitine concentrations were measured in patients with endometrioid-type endometrial cancer (n = 20) and healthy controls (n = 20) who were matched with respect to age and body mass index (BMI).

Results

Stage I endometrial cancer was diagnosed in 12 women (60.0 %) whereas three women (15.0 %) had stage II disease, three women (15.0 %) had stage III disease and two women (10.0 %) had stage IV disease. The healthy controls and endometrial cancer patients were statistically similar in aspect of age, gravidity, parity, BMI, waist-to-thigh ratio, waist-to-hip ratio, menopause, complete blood count parameters, and serum biochemistry. Serum total l-carnitine levels of women with endometrial cancer were significantly lower than those of healthy women (respectively, 5,519.4 ± 2,712.5 vs 7,940.8 ± 3,566.6 ng/dl, p = 0.021). Moreover, serum total l-carnitine levels decreased significantly and progressively with advancing stage (stage I vs II vs III vs IV; 6,294.0 ± 2,885.1 vs 5,800.0 ± 441.2 vs 4,016.0 ± 2,833.3 vs 2,560.0 ± 67.9 ng/dl; p = 0.021).

Conclusions

This is the first study to hypothesize that l-carnitine deficiency participates in the pathogenesis of endometrial cancer by means of a mechanism which is unrelated with obesity and increased amount of fat in human body.

     

Burnout among Primary Care Providers and Staff: Evaluating the Association with Practice Adaptive Reserve and Individual Behaviors

BackgroundWorkplace burnout among healthcare professionals is a critical public health concern. Few studies have examined organizational and individual factors associated with burnout across healthcare professional groups.ObjectiveThe purpose of this study was to examine the association between practice adaptive reserve (PAR) and individual behavioural response to change and burnout among healthcare professionals in primary care.DesignThis cross-sectional study used survey data from 154 primary care practices participating in the EvidenceNOW Heart of Virginia Healthcare initiative.ParticipantsWe analysed data from 1279 healthcare professionals in Virginia. Our sample included physicians, advanced practice clinicians, clinical support staff and administrative staff.Main MeasuresWe used the PAR instrument to measure organizational capacity for change and the Change Diagnostic Index© (CDI) to measure individual behavioural response, which achieved a 76% response rate. Logistic regression analysis was used to estimate the effects of PAR and CDI on burnout.Key ResultsAs organizational capacity for change increased, burnout in healthcare professionals decreased by 51% (OR: 0.49; 95% CI, 0.33, 0.73). As healthcare professionals showed improved response toward change, burnout decreased by 84% (OR: 0.16; 95% CI, 0.11, 0.23). Analysis by healthcare professional type revealed a significant association between high organizational capacity for change, positive response to change and low burnout among administrative staff (OR: 2.92; 95% CI, 1.37, 6.24). Increased hours of work per week was associated with higher odds of burnout (OR: 1.07; 95% CI, 1.05, 1.10) across healthcare professional groups.ConclusionAs transformation efforts in primary care continue, it is critical to understand the influence of these initiatives on healthcare professionals’ well-being. Efforts to reduce burnout among healthcare professionals are needed at both a system and organizational level. Building organizational capacity for change, supporting providers and staff during major change and consideration of individual workload may reduce levels of burnout.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-020-06367-z.KEY WORDS: adaptive reserve, burnout, practice transformation, primary care, well-being     

Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease

Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.Essential tremor is one of the most frequent movement disorders in humans (1). It is characterized primarily by postural or kinetic tremor of the arms and hands, but head, legs, voice, and other regions of the body may also be affected (2). The worldwide prevalence is 0.9%, increasing to more than 4% in elderly populations (1). Familial essential tremor is genetically heterogeneous. Genetic linkage studies of multiply affected families revealed three genomic regions segregating with the condition, on chromosomes 3q13 [ETM1; Online Mendelian Inheritance in Man (OMIM) 190300], 2p22-24 (ETM2; OMIM 602134), and 6p23 (ETM3; OMIM 611456) (3–5). No clearly causal mutations have been identified in these regions, although the common variant DRD3 p.S9G in the ETM1 region has been proposed as a risk factor and HS1BP3 p.A265G in the ETM2 region appeared in two multiply affected families (6, 7). Genomewide association studies of essential tremor reported associations with common variants in an intron of LINGO1 and in an intron of SLC1A2 (8–10). Recently, DNAJC13 p.N855S, which had been identified in Parkinson disease patients, was also found in two unrelated patients with essential tremor (11). Nonsense mutation p.Q290X in the RNA-binding protein FUS was identified by whole exome sequencing in a large family with essential tremor (ETM4; OMIM 614782) (12). Screening other subjects with essential tremor for FUS revealed two rare missense variants, suggesting that mutations in FUS explain a subset of cases with the condition (13, 14).In this study, we examined a six-generation family segregating essential tremor, and in multiple relatives, essential tremor as a feature of Parkinson disease. We carried out whole exome sequencing of genomic DNA from three severely affected family members and subsequent pedigree analysis to identify the genetic basis of essential tremor and Parkinson disease in the family.     

Erythrocyte Deformability and Oxidative Stress in Inflammatory Bowel Disease

Background  

Oxidative stress and reduced microvascular flow are important factors in the pathogenesis of inflammatory bowel disease (IBD). The increased oxidative stress reduces the eriytrocyte deformability. However, in IBD, there are no studies in the literature which evaluate erythrocyte deformability.